title: Immunodominance of HLA-A2-restricted hepatitis C virus-specific CD8+ T cell responses is linked to naive-precursor frequency.
abstract: The impact of naïve-precursor frequency on human virus-specific CD8(+) T cell immunodominance is not well understood. Using a recently developed major histocompatibility complex (MHC) class I tetramer enrichment protocol, we found a conserved hierarchy and a >10-fold difference in naïve-precursor frequencies across three HLA-A2-restricted hepatitis C virus (HCV)-specific epitopes. Importantly, the NS3(1406) epitope with the highest naïve-precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both ex vivo and after in vitro stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve-precursor frequency.
authors.affiliation: University Hospital Freiburg, Department of Medicine II, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schmidt
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumann-Haefelin
authors.forename: Tayibe
authors.initials: T
authors.lastname: Altay
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Volker
authors.initials: V
authors.lastname: Lohmann
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes